Axially chiral N‐(o‐aryl)‐4‐hydroxy‐2‐oxazolidinone derivatives from diastereoselective reduction of N‐(o‐aryl)‐2,4‐oxazolidinediones: Thermally interconvertible atropisomers via ring‐chain‐ring tautomerization

Abstract

The reduction of the axially chiral N-(o-aryl)-5,5-dimethyl-2,4-oxazolidinediones by NaBH(4) yielded axially chiral N-(o-aryl)-4-hydroxy-5,5-dimethyl-2-oxazolidinone enantiomers having a chiral center at C-4, with 100% diastereoselectivity as has been shown by their (1)H and (13)C NMR spectra and by enantioselective HPLC analysis. The resolved enantiomeric isomers were found to interconvert thermally through an aldehyde intermediate formed upon ring cleavage via a latent ring-chain-ring tautomerization. It was found that the rate of enantiomerization depended on the size and the electronic effect of the ortho substituent present on the aryl ring bonded to the nitrogen of the heterocycle.

Synthesis of bis[N-(p-aryl)-carbamoyloxy]alkanes as new low-molecular weight organogelators

“…65,79,80 In this study, we performed some 1 H NMR studies on 3-Me, 3-OMe, 3-Et, 3-OBu, 5-OBu, 3-OHex, and 5-OHex in toluene-d 8 at different temperatures (90 C, 60 C, 30 C) in order to study intermolecular interactions in selfassembled aggregation. As shown in Fig.…”

Solvent‐Catalyzed Ring–Chain–Ring Tautomerization in Axially Chiral Compounds

“…[26] Nevertheless, Roussel et al have claimed that internal rotation does not account for the trend in the activation barriers for some 2-pyrimidinethione derivatives and have suggested a ring-opening-ring-closure mechanism rather than hindered rotation around the N À C aryl bond. [27] In a comprehensive study, Demir-Ordu and Dogan investigated the interconversion between the SM and RP enantiomers of N-(o-aryl)-4-hydroxy-5,5-dimethyl-2-oxazolidinone derivatives 3 (Scheme 1) [12] and proposed a racemization that occurs through a "ring-chain-ring tautomerization" mechanism. [12] To clarify the mechanism, the interconversion of the enantiomer in ethanol was followed by HPLC and the activation barrier for the interconversion of SM into RP was reported to be 25.3 kcal mol À1 .…”

“…[27] In a comprehensive study, Demir-Ordu and Dogan investigated the interconversion between the SM and RP enantiomers of N-(o-aryl)-4-hydroxy-5,5-dimethyl-2-oxazolidinone derivatives 3 (Scheme 1) [12] and proposed a racemization that occurs through a "ring-chain-ring tautomerization" mechanism. [12] To clarify the mechanism, the interconversion of the enantiomer in ethanol was followed by HPLC and the activation barrier for the interconversion of SM into RP was reported to be 25.3 kcal mol À1 . [12] The interconversion was suggested to occur via an acyclic aldehyde intermediate formed by ring-chain tautomerization.…”

“…[12] To clarify the mechanism, the interconversion of the enantiomer in ethanol was followed by HPLC and the activation barrier for the interconversion of SM into RP was reported to be 25.3 kcal mol À1 . [12] The interconversion was suggested to occur via an acyclic aldehyde intermediate formed by ring-chain tautomerization. The aldehyde intermediate, although not observed on the NMR timescale in CDCl 3 , was treated with benzylamine in toluene and trapped in the form of an imine.…”

“…Thus, the presence of the acyclic aldehyde intermediate was verified indirectly by 1 H and 13 C NMR characterization of the cyclic aminal product formed after its treatment with benzylamine in toluene. [12] 2-Oxazolidinone derivatives 3 are heterocyclic analogues of biphenyl atropisomers and have been found to be resolvable by HPLC on a chiral column. These separated enantiomers have the potential to be used as axially chiral catalysts.…”